Involvement of arginine vasopressin and V1b receptor in alcohol drinking in Sardinian alcohol-preferring rats

Background: Recent animal studies have shown that the level of stress-responsive arginine vasopressin (AVP) gene expression in the amygdala is increased during early withdrawal from long-term heroin or cocaine administration. Selective AVP V1b receptor antagonist SSR149415 (capable of exerting antidepressant-like and anxiolytic effects in animal models) also blocked stress-induced reinstatement of drug-seeking behavior. The present study was undertaken to investigate the effects of alcohol and to determine whether: (1) there are genetically determined differences in basal AVP mRNA levels in the medial/central amygdala (Me/CeA) and medial hypothalamus (MH) between selectively bred Sardinian alcohol-preferring (sP) and -nonpreferring (sNP) rats; (2) the AVP mRNA levels are altered by long-term alcohol drinking in sP rats; and (3) V1b receptor antagonist SSR149415 alters alcohol drinking in sP rats. Methods: In Experiment 1, AVP mRNA levels were measured in the Me/CeA and MH of alcohol-naive sP and sNP rats, and sP rats exposed to the the standard, homecage 2-bottle "alcohol vs water" choice regimen, with 24 hours/day for 17 days. In Experiment 2, SSR149415 (3, 10, or 30 mg/kg; i.p.) was acutely administered 30 min before lights off to alcohol-experienced sP rats. Alcohol, water, and food intake were monitored 6 and 24 hours later. Results: We found higher basal AVP mRNA levels in both Me/CeA and MH of alcohol-naive sP than sNP rats; also alcohol consumption decreased AVP mRNA levels in both brain regions of sP rats only, suggesting genetically determined differences between the two rat lines and effects of alcohol drinking in sP rats. Acute treatment with SSR149415 resulted in a significant reduction of alcohol intake in sP rats. Conclusion: The stress-responsive AVP/V1b receptor system is one component of the neural circuitry underlying high alcohol drinking in sP rats.